In pursuit of studies on the regulation of protein synthesis in animal cells, we propose: 1) Further characterization of the heme-reversible eIF-2 alpha kinase, the role of phosphorylation in its activation and the binding of heme to the enzyme in its inactivation. 2) Study of the action of the heme-regulated eIF-2 alpha kinase and of the dsRNA-activated eIF-2 alpha kinase under physiologic conditions in situ in normal animal and human cells and in various human pathologic cells. 3) Study of the mechanisms of reversal of the inhibition of protein synthesis induced by heme-deficiency, dsRNA with and without interferon, and oxidized glutathione, with particular emphasis on exogenous eIF-2, phosphatases, and recently isolated reversing factors. 4) Study of the mechanism of action of glucose-6-phosphate in preventing the activation of an inhibitor of protein synthesis which is active in the presence of heme. 5) Study of the effect of heme on the differentiation of animal cells in culture.